本期节目邀请了密歇根大学病理学教授兼衰老研究中心主任理查德·米勒，他分享了关于干预测试计划（ITP）的最新进展。ITP是一项旨在评估潜在延缓衰老干预措施的计划，研究对象是老鼠。米勒教授介绍了ITP取得的显著成果，包括雷帕霉素、17α-雌二醇和阿卡波糖等药物延长老鼠寿命的成功案例，以及烟酰胺核糖、二甲双胍和白藜芦醇等药物的失败案例。他还深入探讨了衰老生物标志物和衰老速度指标，揭示了关于抗衰老分子的科学见解，并展望了未来研究方向，包括将研究成果从老鼠身上应用到人类身上。

🐭 **ITP的成功与失败：** ITP计划通过对老鼠进行药物干预，旨在延缓衰老过程。该计划取得了一些显著的成果，例如雷帕霉素、17α-雌二醇和阿卡波糖等药物延长了老鼠的寿命。然而，一些药物，如烟酰胺核糖、二甲双胍和白藜芦醇，则未能达到预期效果，这表明延缓衰老的机制十分复杂。

🧬 **衰老速度指标和生物标志物：** ITP计划的研究表明，衰老速度指标可以用来预测个体衰老的快慢。这些指标包括蛋白质组学变化、代谢率变化等。通过研究衰老速度指标，科学家可以更好地理解衰老过程，并开发出更有效的抗衰老药物。

🧪 **从老鼠到人类：** ITP计划的研究成果为人类抗衰老研究提供了宝贵的经验。然而，从老鼠身上获得的成果并不能直接应用到人类身上。科学家们正在努力克服这一挑战，例如通过开发新的药物筛选方法、研究人类衰老速度指标等。

💊 **药物的成功与失败：** ITP计划中，一些药物延长了老鼠的寿命，例如雷帕霉素和17α-雌二醇。而一些药物，如二甲双胍和白藜芦醇，则未能取得预期效果。这表明，药物的有效性不仅取决于其靶点，还取决于其剂量、使用时间等因素。

🔬 **未来方向：** ITP计划的成功为未来抗衰老研究指明了方向。科学家们正在研究新的抗衰老药物，例如靶向衰老细胞的药物、调节代谢的药物等。此外，他们还致力于将研究成果从老鼠身上应用到人类身上，以实现人类健康寿命的延长。

🤔 **反思：** ITP计划的研究结果表明，延缓衰老是一个复杂的挑战。科学家们需要不断探索新的方法，以开发出更有效的抗衰老药物，并最终实现人类健康寿命的延长。

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Richard Miller is a professor of pathology and the Director of the Center for Aging Research at the University of Michigan, as well as a previous guest on The Drive. In this episode, Rich provides an update on the exciting work of the Interventions Testing Program (ITP), an initiative designed to assess potential life-extending interventions in mice. Rich covers the notable successes like rapamycin, 17⍺-estradiol, and acarbose as well as notable failures like nicotinamide riboside, metformin, and resveratrol, providing valuable lessons about the intricacies of the aging process. Rich delves deep into aging biomarkers and aging rate indicators, unraveling crucial insights into the science of geroprotective molecules. Additionally, Rich discusses some surprising successes of recent molecules tested by the ITP and concludes with an optimistic look at future frontiers, including bridging the gap from mice to humans.

We discuss:

An overview of the Interventions Testing Program (ITP) [3:45]; How the mice used by the ITP are superior for research relative to mouse models used in most research [11:15]; Design of ITP studies, outcomes tested, and metrics of interest [19:00]; The process and challenges of drug formulation for mice [30:00]; Four drugs identified by the ITP that extends the lifespan of mice [36:30]; The success of rapamycin and what it tells us about the biology of aging [43:15]; Other measures of healthspan evaluated by the ITP in stage 2 studies [50:45]; Distinguishing aging rate indicators from biomarkers of aging [57:30]; Aging rate indicators identified through the examination of slow-aging mice [59:15]; Why proteomics are essential to understand changes in the cell [1:12:15]; Unraveling aging rate indicators: dose-effect, duration, and future frontiers [1:21:45]; A closer look at aging rate indicators: bridging the gap from mice to humans [1:27:00]; What do laboratory mice die from? [1:38:45]; Distinguishing between a drug that improves an age-sensitive outcome and a drug that improves all aspects of aging [1:42:00]; The ITP study of 17⍺-estradiol: mechanisms of life extension and surprising sex differences [1:43:30]; Unsuccessful drugs studied by the ITP: resveratrol, metformin, and nicotinamide riboside [1:51:30]; Over-the-counter successes in the ITP: meclizine and astaxanthin [2:01:00]; A senolytic drug, fisetin, fails to extend lifespan [2:07:00]; Can targeting senescent cells slow aging? [2:13:00]; Optimism about future findings [2:16:30]; and More.

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